Endothelial Dysfunction in Diabetes

Overview

Journal Biomedicines

Specialty Biomedical Engineering

Date 2020 Jul 3

PMID 32610588

Citations 31

Authors

Yusuke Takeda

Keiichiro Matoba

Kensuke Sekiguchi

Yosuke Nagai

Tamotsu Yokota

Kazunori Utsunomiya

Rimei Nishimura

Affiliations

Soon will be listed here.

Abstract

Diabetes is a worldwide health issue closely associated with cardiovascular events. Given the pandemic of obesity, the identification of the basic underpinnings of vascular disease is strongly needed. Emerging evidence has suggested that endothelial dysfunction is a critical step in the progression of atherosclerosis. However, how diabetes affects the endothelium is poorly understood. Experimental and clinical studies have illuminated the tight link between insulin resistance and endothelial dysfunction. In addition, macrophage polarization from M2 towards M1 contributes to the process of endothelial damage. The possibility that novel classes of anti-hyperglycemic agents exert beneficial effects on the endothelial function and macrophage polarization has been raised. In this review, we discuss the current status of knowledge regarding the pathological significance of insulin signaling in endothelium. Finally, we summarize recent therapeutic strategies against endothelial dysfunction with an emphasis on macrophage polarity.

Citing Articles

Endothelial Dysfunction and Oxidative Stress in Patients with Severe Coronary Artery Disease: Does Diabetes Play a Contributing Role?.

Boieriu A, Luca C, Neculoiu C, Bisoc A, Tint D Medicina (Kaunas). 2025; 61(1).

PMID: 39859119 PMC: 11767194. DOI: 10.3390/medicina61010135.

Endothelial Dysfunction and Cardiovascular Disease: Hyperbaric Oxygen Therapy as an Emerging Therapeutic Modality?.

Batinac T, Baticic L, Krsek A, Knezevic D, Marcucci E, Sotosek V J Cardiovasc Dev Dis. 2024; 11(12).

PMID: 39728298 PMC: 11677558. DOI: 10.3390/jcdd11120408.

The effect and mechanism of freeze-dried powder of on improving inflammatory injury of rat glomerular mesangial cells through TXNIP / NLRP3 pathway.

Sun X, Mijiti M, Huang C, Mei S, Fang K, Yang Y Heliyon. 2024; 10(18):e38206.

PMID: 39364251 PMC: 11447352. DOI: 10.1016/j.heliyon.2024.e38206.

Licorice Extract Isoliquiritigenin Protects Endothelial Function in Type 2 Diabetic Mice.

Wang L, Zhu R, He C, Li H, Zhang Q, Cheung Y Nutrients. 2024; 16(18).

PMID: 39339760 PMC: 11435099. DOI: 10.3390/nu16183160.

The Effect of Statins on Carotid Intima-Media Thickness and C-Reactive Protein in Type 2 Diabetes Mellitus: A Meta-Analysis.

Mashaba G, Phoswa W, Mokgalaboni K J Cardiovasc Dev Dis. 2024; 11(9).

PMID: 39330333 PMC: 11432595. DOI: 10.3390/jcdd11090276.

References

Erdogdu O, Nathanson D, Sjoholm A, Nystrom T, Zhang Q . Exendin-4 stimulates proliferation of human coronary artery endothelial cells through eNOS-, PKA- and PI3K/Akt-dependent pathways and requires GLP-1 receptor. Mol Cell Endocrinol. 2010; 325(1-2):26-35. DOI: 10.1016/j.mce.2010.04.022. View

Charo I . Macrophage polarization and insulin resistance: PPARgamma in control. Cell Metab. 2007; 6(2):96-8. DOI: 10.1016/j.cmet.2007.07.006. View

Zhuge F, Ni Y, Nagashimada M, Nagata N, Xu L, Mukaida N . DPP-4 Inhibition by Linagliptin Attenuates Obesity-Related Inflammation and Insulin Resistance by Regulating M1/M2 Macrophage Polarization. Diabetes. 2016; 65(10):2966-79. DOI: 10.2337/db16-0317. View

Lawlor M, Alessi D . PKB/Akt: a key mediator of cell proliferation, survival and insulin responses?. J Cell Sci. 2001; 114(Pt 16):2903-10. DOI: 10.1242/jcs.114.16.2903. View

Varin E, Mulvihill E, Beaudry J, Pujadas G, Fuchs S, Tanti J . Circulating Levels of Soluble Dipeptidyl Peptidase-4 Are Dissociated from Inflammation and Induced by Enzymatic DPP4 Inhibition. Cell Metab. 2018; 29(2):320-334.e5. DOI: 10.1016/j.cmet.2018.10.001. View

Drucker D . Incretin action in the pancreas: potential promise, possible perils, and pathological pitfalls. Diabetes. 2013; 62(10):3316-23. PMC: 3781450. DOI: 10.2337/db13-0822. View

Bender S, Laughlin M . Modulation of endothelial cell phenotype by physical activity: impact on obesity-related endothelial dysfunction. Am J Physiol Heart Circ Physiol. 2015; 309(1):H1-8. PMC: 4491515. DOI: 10.1152/ajpheart.00177.2015. View

Nafisa A, Gray S, Cao Y, Wang T, Xu S, Wattoo F . Endothelial function and dysfunction: Impact of metformin. Pharmacol Ther. 2018; 192:150-162. DOI: 10.1016/j.pharmthera.2018.07.007. View

Avogaro A, Albiero M, Menegazzo L, De Kreutzenberg S, Fadini G . Endothelial dysfunction in diabetes: the role of reparatory mechanisms. Diabetes Care. 2011; 34 Suppl 2:S285-90. PMC: 3632194. DOI: 10.2337/dc11-s239. View

10.

Kajikawa M, Maruhashi T, Hidaka T, Matsui S, Hashimoto H, Takaeko Y . Effect of Saxagliptin on Endothelial Function in Patients with Type 2 Diabetes: A Prospective Multicenter Study. Sci Rep. 2019; 9(1):10206. PMC: 6629702. DOI: 10.1038/s41598-019-46726-3. View

11.

Snyder S, Jaffrey S . Vessels vivified by Akt acting on NO synthase. Nat Cell Biol. 1999; 1(4):E95-6. DOI: 10.1038/12093. View

12.

Corretti M, Anderson T, Benjamin E, Celermajer D, Charbonneau F, Creager M . Guidelines for the ultrasound assessment of endothelial-dependent flow-mediated vasodilation of the brachial artery: a report of the International Brachial Artery Reactivity Task Force. J Am Coll Cardiol. 2002; 39(2):257-65. DOI: 10.1016/s0735-1097(01)01746-6. View

13.

Fujii N, Reinke M, Brunt V, Minson C . Impaired acetylcholine-induced cutaneous vasodilation in young smokers: roles of nitric oxide and prostanoids. Am J Physiol Heart Circ Physiol. 2013; 304(5):H667-73. PMC: 3602751. DOI: 10.1152/ajpheart.00731.2012. View

14.

Kharbanda R, Walton B, Allen M, Klein N, Hingorani A, MacAllister R . Prevention of inflammation-induced endothelial dysfunction: a novel vasculo-protective action of aspirin. Circulation. 2002; 105(22):2600-4. DOI: 10.1161/01.cir.0000017863.52347.6c. View

15.

Zandi S, Nakao S, Chun K, Fiorina P, Sun D, Arita R . ROCK-isoform-specific polarization of macrophages associated with age-related macular degeneration. Cell Rep. 2015; 10(7):1173-86. PMC: 5219927. DOI: 10.1016/j.celrep.2015.01.050. View

16.

Hamburg N, Palmisano J, Larson M, Sullivan L, Lehman B, Vasan R . Relation of brachial and digital measures of vascular function in the community: the Framingham heart study. Hypertension. 2011; 57(3):390-6. PMC: 3049726. DOI: 10.1161/HYPERTENSIONAHA.110.160812. View

17.

Davis B, Xie Z, Viollet B, Zou M . Activation of the AMP-activated kinase by antidiabetes drug metformin stimulates nitric oxide synthesis in vivo by promoting the association of heat shock protein 90 and endothelial nitric oxide synthase. Diabetes. 2006; 55(2):496-505. DOI: 10.2337/diabetes.55.02.06.db05-1064. View

18.

Helmstadter J, Frenis K, Filippou K, Grill A, Dib M, Kalinovic S . Endothelial GLP-1 (Glucagon-Like Peptide-1) Receptor Mediates Cardiovascular Protection by Liraglutide In Mice With Experimental Arterial Hypertension. Arterioscler Thromb Vasc Biol. 2019; 40(1):145-158. PMC: 6946108. DOI: 10.1161/atv.0000615456.97862.30. View

19.

Lumeng C, Bodzin J, Saltiel A . Obesity induces a phenotypic switch in adipose tissue macrophage polarization. J Clin Invest. 2007; 117(1):175-84. PMC: 1716210. DOI: 10.1172/JCI29881. View

20.

Corgnali M, Piconi L, Ihnat M, Ceriello A . Evaluation of gliclazide ability to attenuate the hyperglycaemic 'memory' induced by high glucose in isolated human endothelial cells. Diabetes Metab Res Rev. 2007; 24(4):301-9. DOI: 10.1002/dmrr.804. View